Genetic losses and duplications may cause schizophrenia

30 July 2008

A proportion of people suffering from schizophrenia have loss or duplication of regions of their chromosomes that significantly increase risk of the disease, according to new findings from a large multinational research group published today in ‘Nature’.

The research group, known as the International Schizophrenia Consortium, studied 3,391 cases of schizophrenia and 3,181 comparison subjects. They found that one per cent of the people with schizophrenia had large deletions and duplications on chromosomes 1, 15 and 22. The consortium, from Europe and the USA, was initially organised by Professor Hugh Gurling at UCL Mental Health Sciences and Dr Pamela Sklar at Harvard University. Their study is the largest and most complete of its type to date.

Schizophrenia is a common and often devastating brain disorder diagnosed by observing the symptoms of abnormal beliefs, bizarre behaviour, hearing voices, change in personality, difficulty concentrating on tasks, poor cognitive performance and often lack of self care. It affects approximately 1 person in 100. The onset is usually during the teens and the illness can have a tragic effect on the whole of someone’s life. All available treatments are limited by unacceptable side effects. The hope for the future relies strongly on understanding the underlying genetic causes and by designing new drugs based on the brain proteins and their systems that have been disturbed by genetic effects. 

Professor Gurling said: “Finding so many large and small deletions and duplications was no surprise because we have known for many years that schizophrenia is highly genetic. The surprise was how efficiently and quickly the new technology of studying genes using microarrays has propelled our understanding of schizophrenia. Our knowledge about this disorder has been revolutionised and the text books on psychiatry now need rewriting.”

Formed in 2006, the International Schizophrenia Consortium is led by senior researchers from 11 institutes in Europe and the USA.  The investigators used new genomic technologies and novel analytical techniques developed at the Broad Institute USA to screen these samples for structural variants in the genome, sites where a portion of a chromosome is missing or duplicated. “The consortium should be recognised for taking the important first step towards unearthing the full underlying genomic architecture of schizophrenia and other psychotic disorders,” said Edward Scolnick, MD, Director of the Stanley Center for Psychiatric Research at the Broad Institute.  “Only by doing such a large study could we have uncovered these stunning findings to such a high degree of confidence, thus setting the stage for an even more complete understanding of the full genomic contributions to disease. This study could only have been done with the open collaboration of many individuals and institutions dedicated to understanding – and treating – this terrifying disease.”

To find out more about Professor Gurling and UCL Mental Health Sciences, and to see the article in ‘Nature’, use the links at the top of the article.